Biotinidase deficiency is a genetic, treatable, metabolic condition that is caused by the levels of an enzyme called biotinidase being too low or absent in an affected individual. Having less biotinidase enzyme activity than needed causes the body to not be able to use the vitamin biotin (sometimes referred to as vitamin H) appropriately by the body. Biotin is used by the body to assist in the break down of proteins, fats and carbohydrates from the food we eat to make them usable by the body. When biotinidase enzyme activity is too low, there is not enough biotin available in the body for proper metabolism of the food we eat.
Biotinidase deficiency is classified as partial or profound, based on how much biotinidase enzyme activity is present in the body. Individuals with untreated biotinidase deficiency may develop problems such as hypotonia (low muscle tone), eczema (skin rash), alopecia (hair loss), seizures, developmental delay, breathing problems, ataxia (balance, coordination and movement problem), candidiasis (a type of fungal infection), lactic aciduria (presence of high levels of lactic acid in the urine), hyperammonemia (higher than normal levels of ammonia in the blood), hearing loss, conjunctivitis (pink eye), lethargy (drowsiness or low energy), coma (period of unconsciousness), vomiting, diarrhea, hepatomegaly (enlarged liver), splenomegaly (enlarged spleen), speech problems and developmental delay.
Treatment of biotinidase deficiency is lifelong daily oral supplementation with free biotin. Many symptoms of untreated biotinidase deficiency are expected to improve with initiation of treatment, and since most newborns are screened for biotinidase deficiency as part of newborn screening programs, treatment is often started prior to the initiation of symptoms. Individuals with biotinidase deficiency who are appropriately treated prior to symptoms developing can be expected to remain asymptomatic.
Biotinidase deficiency is inherited in an autosomal recessive manner, and unaffected family members of affected individuals can be tested to determine their carrier status/reproductive risks for biotinidase deficiency.
Biotinidase deficiency is most often referred to as biotinidase deficiency, classified as either profound or partial. Other names for biotinidase deficiency may also include:
BTD
BTD deficiency
BIOT
Infantile multiple carboxylase deficiency
Juvenile multiple carboxylase deficiency
Late-onset multiple carboxylase deficiency
Multiple carboxylase deficiency, due to biotinidase deficiency
Late-onset biotin-responsive multiple carboxylase deficiency
Approximately 1 in 60,000 babies are born with a form of biotinidase deficiency (profound or partial). More specifically, worldwide the incidence of profound biotinidase deficiency has been estimated at 1 in 137,401, partial biotinidase deficiency 1 in 109,921, and combined incidence of profound and partial biotinidase deficiency 1 in 61,067.
Biotinidase deficiency is more common in areas with a high rate of consanguinity (individuals who are blood relatives having children together, for example, first cousin marriages) such as Turkey and Saudi Arabia. The incidence of biotinidase deficiency also appears to be increased in Hispanic populations and lower in African American populations.
Biotinidase deficiency is most often referred to as biotinidase deficiency, but is further classified as profound biotinidase deficiency or partial biotinidase deficiency, depending on the amount of biotinidase enzyme activity present in the individual. Profound biotinidase deficiency results from less working enzyme than partial biotinidase deficiency, and is a more severe condition if untreated.
Biotinidase deficiency may commonly be abbreviated BTD or BTD deficiency, or BIOT. BTD is also the name of the gene changed in biotinidase deficiency.
Frequently Asked Questions About Biotinidase deficiency
Why is biotinidase deficiency caused by BTD gene changes?
The BTD gene is responsible for making an enzyme called biotinidase. The biotinidase enzyme is responsible for releasing a specific B vitamin known as biotin that is bound to proteins in some foods. When biotin is unbound by the biotinidase enzyme, it is known as free biotin. Free biotin is used in the body by a group of enzymes known as biotin-dependent carboxylases. Biotin-dependent carboxylases are used to break down proteins, fats, and carbohydrates from the food we eat to make them usable by the body. A lack of normal biotinidase enzyme activity leads to biotin not being appropriately unbound and biotin-dependent carboxylases cannot work properly.
More information about how changes in the BTD gene cause biotinidase deficiency can be found at Genetics Home Reference or GeneReviews
Who else in my family should I test for biotinidase deficiency?
Once an individual has been diagnosed with biotinidase deficiency, evaluation of other family members is appropriate to determine if other members of a family are affected with or carriers of biotinidase deficiency. Since biotinidase deficiency is inherited in an autosomal recessive manner, the parents of an affected individual are each expected to be at a minimum carriers of biotinidase deficiency (or affected). If the parents are both carriers, then full siblings of an affected individual have a ¼ (25%) chance of being affected. Children of an affected individual will all be carriers of biotinidase deficiency and would be at risk of being affected or not depending upon the carrier status of their other parent. Unaffected siblings of an affected individual’s parents (the affected individual’s aunts and uncles) have a ½ (50%) chance of being a carrier of biotinidase deficiency.
Genetic counselors can assist a family in determining who in the family should be tested for biotinidase deficiency through the construction of a pedigree, or family tree. To locate a genetic counselor near you, you can consult the "Find A Genetic Counselor" searchable online directory on the National Society of Genetic Counselors website to locate genetic counselors throughout the United States and Canada.
Where can I find more information about biotinidase deficiency?
Connecting with other families who are caring for individuals with biotinidase deficiency can be a helpful source of information and support for individuals with or caretakers of individuals diagnosed with biotinidase deficiency. The Biotinidase Deficiency Family Support Group is a non-profit volunteer organization. It’s mission as listed on the website is "to establish a forum to exchange information about biotinidase deficiency among affected individuals and with medical professionals and to advocate for the inclusion of biotinidase testing in all newborn screening programs."
More information about biotinidase deficiency can be obtained from the following sources:
What specialist doctors should I see if I have biotinidase deficiency?
Regular contact with a geneticist or metabolic specialist can help an individual with biotinidase deficiency with the ongoing treatment and management of biotinidase deficiency, and also identify any other specialists that should be seen.
In addition to ongoing lifelong treatment with oral free biotin, individuals with biotinidase deficiency should have yearly vision and hearing evaluations and regular physical examination by a doctor or metabolic specialist familiar with biotinidase deficiency. Individuals with biotinidase deficiency should be monitored by their physician for symptoms of biotinidase deficiency such as vision or hearing problems, skin problems, and developmental problems, as early interventions for any potential symptoms may improve outcome.
To assist in locating genetic services in your area, the National Society of Genetic Counselors website includes a searchable "Find A Genetic Counselor" directory which may be used to locate genetic counselors throughout the United States and Canada. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website. If you are looking for a metabolic clinic for treatment in the United States, you can search for the clinic or clinics in your state.
A metabolic dietician can be found through the Genetic Metabolic Dieticians International webpage.
What kind of form does free biotin come in?
Biotin generally comes as a tablet or capsule, which can be swallowed intact by an older child or adult. To administer biotin to an infant or young child who cannot swallow a tablet or capsule, it is recommended that a tablet be crushed/a capsule be opened and mixed with a small amount of breast milk or formula in a spoon, medicine dispenser, or syringe. It is recommended that the biotin not be put in a bottle, but rather in a small amount of liquid that can be consumed in full all at once.
What is the usual abbreviation for biotinidase deficiency?
Biotinidase deficiency may commonly be abbreviated BTD or BTD deficiency, or BIOT. BTD is also the name of the gene changed in biotinidase deficiency.
What is the chromosome location for the gene that causes biotinidase deficiency?
Changes in the BTD gene are responsible for causing biotinidase deficiency. The BTD gene is located at chromosome location 3p25.1.
What is the chance that I am a carrier of biotinidase deficiency?
If you do not have a family member with biotinidase deficiency or any reason to suspect that you might be affected with biotinidase deficiency, then the general population based chances that an individual is a carrier of biotinidase deficiency is estimated to be approximately 1 in 120 (0.8%).
What is biotinidase deficiency?
Biotinidase deficiency is a genetic, treatable, metabolic condition that is caused by the levels of an enzyme called biotinidase being too low or absent in an affected individual. Having less biotinidase enzyme activity than needed causes the body to not be able to use the vitamin biotin (sometimes referred to as vitamin H) appropriately by the body. Biotin is used by the body to assist in the break down of proteins, fats and carbohydrates from the food we eat to make them usable by the body. When biotinidase enzyme activity is too low, there is not enough biotin available in the body for proper metabolism of the food we eat.
Biotinidase deficiency is classified as partial or profound, based on how much biotinidase enzyme activity is present in the body. Individuals with untreated biotinidase deficiency may develop problems such as hypotonia (low muscle tone), eczema (skin rash), alopecia (hair loss), seizures, developmental delay, breathing problems, ataxia (balance, coordination and movement problem), candidiasis (a type of fungal infection), lactic aciduria (presence of high levels of lactic acid in the urine), hyperammonemia (higher than normal levels of ammonia in the blood), hearing loss, conjunctivitis (pink eye), lethargy (drowsiness or low energy), coma (period of unconsciousness), vomiting, diarrhea, hepatomegaly (enlarged liver), splenomegaly (enlarged spleen), speech problems and developmental delay.
Treatment of biotinidase deficiency is lifelong daily oral supplementation with free biotin. Many symptoms of untreated biotinidase deficiency are expected to improve with initiation of treatment, and since most newborns are screened for biotinidase deficiency as part of newborn screening programs, treatment is often started prior to the initiation of symptoms. Individuals with biotinidase deficiency who are appropriately treated prior to symptoms developing can be expected to remain asymptomatic.
Biotinidase deficiency is inherited in an autosomal recessive manner, and unaffected family members of affected individuals can be tested to determine their carrier status/reproductive risks for biotinidase deficiency.
What is biotinidase deficiency called most often by doctors?
Biotinidase deficiency is most often referred to as biotinidase deficiency, but is further classified as profound biotinidase deficiency or partial biotinidase deficiency, depending on the amount of biotinidase enzyme activity present in the individual. Profound biotinidase deficiency results from less working enzyme than partial biotinidase deficiency, and is a more severe condition if untreated.
What health problems should I look for in biotinidase deficiency?
It is recommended that individuals with biotinidase deficiency have lifelong treatment with biotin supplementation. Individuals with treated biotinidase deficiency should have yearly vision and hearing evaluations and regular physical examination by a doctor or metabolic specialist familiar with biotinidase deficiency.
In addition to ongoing treatment with biotin supplementation, individuals with biotinidase deficiency should be monitored by their physician for symptoms of biotinidase deficiency such as vision or hearing problems, skin problems, and developmental problems, as early interventions with any potential symptoms may improve outcome.
To assist in locating genetic services in your area, the National Society of Genetic Counselors website includes a searchable "Find A Genetic Counselor" directory which may be used to locate genetic counselors throughout the United States and Canada.
What gene change causes biotinidase deficiency?
Biotinidase deficiency is caused by changes in the BTD gene. The BTD gene is responsible for making an enzyme called biotinidase. Biotinidase deficiency-related BTD gene changes lead to lower than usual (or completely absent) amounts of biotinidase activity in the body.
More information about the BTD gene can be found at Genetics Home Reference or GeneReviews.
What are the main symptoms of biotinidase deficiency?
When diagnosed early and appropriately treated with biotin supplementation, individuals with biotinidase deficiency are often asymptomatic. When biotinidase deficiency is diagnosed by newborn screening, treatment may be started prior to symptoms ever appearing in an individual, and ongoing appropriate treatment with biotin supplementation can be expected to prevent the occurrence of any symptoms.
Individuals with untreated partial biotinidase deficiency (10-30% of normal enzyme activity present) may only develop symptoms when their bodies are under a form of stress, such as with an illness or infection. Symptoms in untreated partial biotinidase deficiency may include hypotonia (low muscle tone), eczema (skin rash) and alopecia (hair loss).
Individuals with untreated profound biotinidase deficiency (<10% normal enzyme activity) are expected to develop symptoms in the first weeks to months of life. Symptoms of untreated profound biotinidase deficiency may include hypotonia (low muscle tone), seizures, alopecia (hair loss), eczema (form of skin rash), developmental delay, breathing problems, ataxia (balance, coordination and movement problem), candidiasis (a type of fungal infection), lactic aciduria (presence of high levels of lactic acid in the urine), hyperammonemia (higher than normal levels of ammonia in the blood), hearing loss, conjunctivitis (pink eye), lethargy (drowsiness or low energy), coma (period of unconsciousness), vomiting, diarrhea, hepatomegaly (enlarged liver), splenomegaly (enlarged spleen), speech problems and developmental delay.
To learn more about the symptoms of biotinidase deficiency, talk with your doctor or consult with a genetic counselor. The National Society of Genetic Counselors website includes a "Find a Genetic Counselor" search tool which can help you locate a genetic counselor in the United States or Canada.
What are the first steps after an initial diagnosis of biotinidase deficiency?
Asymptomatic babies diagnosed with biotinidase deficiency through newborn screening or on the basis of family history should have the following evaluations performed:
What are the chances that I will have a child with biotinidase deficiency?
If you do not have a family member with biotinidase deficiency or any reason to suspect that you might be affected with biotinidase deficiency, then the general population based chances that an individual is a carrier of biotinidase deficiency is estimated to be approximately 1 in 120 (0.8%). If both members of a couple each have an approximately 1 in 120 chance to be a carrier of biotinidase deficiency, then they would have an approximately 1 in 57,600 chance of having a child affected with biotinidase deficiency (1/120 x 1/120 x ¼).
Should pregnant women whose babies might have biotinidase deficiency do anything different during their pregnancies?
It has been suggested by some that pregnant women whose babies are known to have or are at risk to have biotinidase deficiency take biotin supplementation during the pregnancy. However, as of October of 2016, there has not been a determination of an optimal prenatal dose of biotin supplementation for pregnant women and so to our knowledge there are no standardized recommendations for biotin supplementation during pregnancy for affected/at risk babies.
Should carriers of biotinidase deficiency have treatment?
Individuals who carry a single copy of a profound or partial biotinidase deficiency BTD gene change are not at risk for any health problems related to biotinidase deficiency, do not require treatment and do not need to take supplemental oral free biotin.
My partner and I are both carriers of biotinidase deficiency. Is preimplantation genetic diagnosis (PGD) for biotinidase deficiency possible?
If both members of a couple are known to be carriers of biotinidase deficiency and their specific biotinidase deficiency-related BTD gene changes are known, in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD) for biotinidase deficiency is possible. This would enable identifying embryos not affected with biotinidase deficiency prior to implantation and only transferring embryos for possible pregnancy which are unaffected. It is recommended that prenatal testing through chorionic villus sampling (CVS) or amniocentesis be done to confirm the preimplantation genetic test results in pregnancies conceived through IVF with PGD.
There may be differences of opinion amongst medical professionals and between individuals about whether IVF with PGD for biotinidase deficiency, while technically possible, is warranted or not. Genetic counselors can provide valuable information and support during decision making for individuals considering reproductive options. To locate genetic counseling services, you can use the searchable "Find A Genetic Counselor" directory on the National Society of Genetic Counselors website to locate genetic counselors throughout the United States and Canada.
My partner and I are both carriers of biotinidase deficiency. Can I find out before birth if my baby is affected?
If both members of a couple are known to be carriers of biotinidase deficiency and their specific biotinidase deficiency-related BTD gene changes are known, prenatal testing through chorionic villus sampling (CVS) or amniocentesis is an option to test for the presence or absence of biotinidase deficiency-related BTD gene changes in a baby before birth. It is also possible to measure biotinidase enzyme activity in cells obtained by amniocentesis, but molecular testing (looking for the specific BTD gene changes) is the preferred method for prenatal testing.
There may be differences of opinion amongst medical professionals and between individuals about whether genetic testing for biotinidase deficiency before birth, while technically possible, is warranted or not. Genetic counselors can provide valuable information and support during decision making for individuals considering reproductive testing options. To locate genetic counseling services, you can use the searchable "Find A Genetic Counselor" directory on the National Society of Genetic Counselors website to locate genetic counselors throughout the United States and Canada.
Is there routine newborn testing for biotinidase deficiency?
Most newborns born in the United States have newborn screening, and biotinidase deficiency is a recommended condition to be included in routine newborn screening. If you have questions about what conditions your state screens newborns for, and whether biotinidase deficiency is included, the Save Babies through Screening website provides links to state specific newborn screening information.
If you are concerned that your newborn may have biotinidase deficiency and/or wonder whether newborn screening for biotinidase deficiency was performed on your baby, please talk with your child’s pediatrician about your concerns and how to get more information about the possibility of testing or further evaluation.
Is there more than one test for biotinidase deficiency?
Biotinidase deficiency can be confirmed by either biochemical or molecular testing on blood.
For biochemical testing for biotinidase deficiency, the amount of biotinidase enzyme activity is measured in the blood. Individuals with biotinidase activity less than 10% of the normal average are diagnosed with profound biotinidase deficiency, while individuals with biotinidase activity 10-30% of the normal average are diagnosed with partial biotinidase deficiency. The diagnosis of profound or partial biotinidase deficiency can be made by biochemical (enzyme) testing alone.
Molecular testing can also be used to diagnose biotinidase deficiency. The BTD gene is the name of the gene involved in biotinidase deficiency, and spelling errors in the BTD gene detected by sequencing of the gene are found in approximately 99% of individuals with biotinidase deficiency. BTD gene deletion/duplication can be done if gene sequencing does not identify two gene changes in affected individuals.
Genetic counselors may help you understand your testing options for biotinidase deficiency. The National Society of Genetic Counselors website includes a searchable "Find A Genetic Counselor" online directory to assist you in locating genetic counselors throughout the United States and Canada.
Is there clinical research going on for biotinidase deficiency?
For the most up to date clinical trials for biotinidase deficiency, visit clinicaltrials.gov . As of July 2019, there were four completed trials listed.
Is there a treatment for biotinidase deficiency?
Biotinidase deficiency is treated by lifelong supplementation with oral biotin daily. Symptomatic individuals with profound biotinidase deficiency are expected to improve with the initiation of biotin therapy, and asymptomatic individuals who are diagnosed by newborn screening or through other methods prior to onset of symptoms and have appropriate ongoing treatment can be expected to avoid developing symptoms.
Oral biotin for the treatment of biotinidase deficiency is generally dosed at 5-10 mg per day. Oral biotin may also be referred to as vitamin H, coenzyme R, or part of vitamin B complex, and is available over the counter as a dietary supplement. However, for the treatment of biotinidase deficiency, it is important that the biotin is in the form of free biotin, as opposed to bound biotin. The biotin contained in oral multivitamin supplements is generally in the form of bound biotin, and is not effective or appropriate for treatment of biotinidase deficiency. Biotin is available in the free form in over the counter supplements. It is important that if you are giving biotin to your child for the purpose of treating biotinidase deficiency that you ensure that the biotin that you are giving is in the free (unbound) form. Your doctor or pharmacist may be able to assist you with any questions about this issue.
In addition to ongoing, lifelong treatment with oral free biotin supplements, individuals with symptoms related to biotinidase deficiency may benefit from symptomatic management with appropriate specialists.
Individuals with treated biotinidase deficiency should have yearly vision and hearing evaluations and regular physical examination by a doctor or metabolic specialist familiar with biotinidase deficiency. Individuals with biotinidase deficiency should be monitored by their physician for symptoms of biotinidase deficiency such as vision or hearing problems, skin problems, and developmental problems, as early intervention for any potential symptoms may improve outcome.
The best way to obtain the most accurate, current, clear, and comprehensive information about treatment and management of biotinidase deficiency is to be seen by a geneticist or metabolic specialist. Geneticists/metabolic specialists and genetic counselors work as a team to answer your questions, discuss testing, identify your at-risk family members, and develop a comprehensive evaluation and treatment plan for you. They will work with your current doctors to organize the treatment, tests, and specialists you need.
To assist in locating genetic services in your area, the National Society of Genetic Counselors website includes a searchable "Find A Genetic Counselor" directory which may be used to locate genetic counselors throughout the United States and Canada. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website .
Is biotinidase deficiency life-threatening?
Untreated biotinidase deficiency can lead to multiple health problems, including some that are life threatening. However, lifelong treatment with daily oral free biotin is effective in improving many of the symptoms an affected individual may experience. Since most babies are screened for biotinidase deficiency by newborn screening and therefore treatment can be started in infancy prior to the initiation of any serious symptoms, it is expected that asymptomatic treated individuals who continue their treatment will continue to be asymptomatic and not develop any complications, including any life-threatening concerns, potentially associated with untreated biotinidase deficiency.
Is biotinidase deficiency curable?
Lifelong daily oral free biotin supplementation is an extremely effective treatment for biotinidase deficiency, but it is not a cure. Treated individuals continue to have low or absent biotinidase enzyme activity lifelong, and to avoid developing symptoms or complications from biotinidase deficiency, it is necessary that daily oral free biotin supplementation is continued lifelong.
If you have biotinidase deficiency, will you always show symptoms?
When diagnosed early and appropriately treated with biotin supplementation, individuals with biotinidase deficiency are often asymptomatic. When biotinidase deficiency is diagnosed by newborn screening, treatment may be started prior to symptoms ever appearing in an individual, and ongoing appropriate treatment with biotin supplementation can be expected to prevent the occurrence of any symptoms.
Once an individual with untreated biotinidase deficiency becomes symptomatic, initiation of appropriate ongoing treatment with biotin supplementation can be expected to improve or eliminate some symptoms of biotinidase deficiency. However, not all symptoms of untreated biotinidase deficiency can always be reversed even with biotin therapy, making early diagnosis and treatment of biotinidase deficiency important.
If you are concerned that you or your child may have symptoms of biotinidase deficiency, you should consult with your doctor or locate genetic services in your area. The National Society of Genetic Counselors website includes a "Find A Genetic Counselor" search tool which can help you locate a genetic counselor in the United States or Canada.
If I have had one child with biotinidase deficiency, what are the chances that another child will also be affected with biotinidase deficiency?
If you and your partner are unaffected with biotinidase deficiency but you have had a child with biotinidase deficiency, it is likely that you and your partner are both carriers of a biotinidase deficiency-related BTD gene change. If both members of a couple are carriers of a biotinidase deficiency-related BTD gene change, then with every pregnancy between them there is a ¼ (25%) chance of the baby being affected with biotinidase deficiency, a ½ (50%) chance of the baby being a carrier of a single biotinidase deficiency-related gene change, and a ¼ (25%) chance of the baby being neither affected nor a carrier of biotinidase deficiency.
Genetic testing is available to confirm that both you and your partner are carriers of biotinidase deficiency, as would be expected once you have had an affected child. If you have questions about genetic testing options, or about your reproductive risks and options related to biotinidase deficiency, you can locate genetic counselors throughout the United States and Canada on the "Find A Genetic Counselor" searchable directory on the National Society of Genetic Counselors website.
If I have biotinidase deficiency, what should my doctor know about managing the disease?
Individuals with biotinidase deficiency require lifelong treatment with oral free biotin supplementation. In addition to ensuring that an affected individual is appropriately treated with free biotin supplementation, the physician caring for an individual with biotinidase deficiency should ensure that he or she have yearly vision and hearing evaluations and regular physical examination by a doctor or metabolic specialist familiar with biotinidase deficiency. Individuals with biotinidase deficiency should be monitored by their physician for symptoms of biotinidase deficiency such as vision or hearing problems, skin problems, and developmental problems, as early interventions with any potential symptoms may improve outcome.
Geneticists and metabolic specialists have specialized training and expertise in managing the care of individuals with inherited metabolic conditions, including biotinidase deficiency. Geneticists/metabolic specialists and genetic counselors work as a team to answer your questions, discuss testing, identify your at-risk family members, and develop a comprehensive evaluation and treatment plan for you. They will work with your current doctors to organize the treatment, tests, and specialists you need.
To assist in locating genetic services in your area, the National Society of Genetic Counselors website includes a searchable "Find A Genetic Counselor" directory which may be used to locate genetic counselors throughout the United States and Canada. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website. If you are looking for a metabolic clinic for treatment in the United States, you can search for the clinic or clinics in your state.
A metabolic dietician can be found through the Genetic Metabolic Dieticians International webpage.
I’m thinking about having a baby. Can I find out if I am a carrier of biotinidase deficiency?
If you do not have a family history of individuals known to be affected with or carriers of biotinidase deficiency, then your chances of being a carrier of biotinidase deficiency (general population rate) is approximately 1 in 120. While technically possible to do, carrier screening specifically for biotinidase deficiency is not generally offered/recommended during pregnancy. However, it is becoming increasingly common for individuals to be offered the option of carrier screening for a wide variety of genetic conditions prior to or during pregnancy (referred to as Universal Carrier Screening), and some biotinidase deficiency-related gene changes may be included on Universal Carrier Screening panels.
Genetic counselors can help you understand your reproductive risks and options, including preconception or prenatal carrier screening and genetic testing options. To locate genetic counseling services, you can use the searchable "Find A Genetic Counselor" directory on the National Society of Genetic Counselors website to locate genetic counselors throughout the United States and Canada.
I have biotinidase deficiency. What are the chances that my children will also be affected?
If you are affected with biotinidase deficiency, then both copies of your BTD gene have a biotinidase deficiency-related gene change and all of your children will receive a biotinidase deficiency-related BTD gene change from you and at a minimum be carriers of biotinidase deficiency. Whether or not your children may be affected with biotinidase deficiency will depend upon the carrier status of your reproductive partner. If your partner is unaffected with biotinidase deficiency and also not a carrier, then all of your children will inherit a biotinidase deficiency-related BTD gene change from you and a working copy of the BTD gene from your partner and be unaffected carriers of biotinidase deficiency. If your partner is an unaffected carrier of biotinidase deficiency, then all of your children will inherit a biotinidase deficiency-related BTD gene change from you and will either inherit your partner’s working copy of the BTD gene and be carriers of biotinidase deficiency or your partner’s biotinidase deficiency-related BTD gene change and be affected with biotinidase deficiency (1/2 or 50% chance of either outcome with each pregnancy). If your partner is also affected with biotinidase deficiency, then all of your children will inherit a biotinidase deficiency-related gene change from each of you and all of your children would be expected to have biotinidase deficiency.
It is possible for an individual who wants to know their carrier status for biotinidase deficiency to have genetic testing. If you have questions about genetic testing options, or about your reproductive risks and options related to biotinidase deficiency, you can locate genetic counselors throughout the United States and Canada on the "Find A Genetic Counselor" searchable directory on the National Society of Genetic Counselors website.
How many people have biotinidase deficiency?
Approximately 1 in 60,000 babies are born with a form of biotinidase deficiency (profound or partial). More specifically, worldwide the incidence of profound biotinidase deficiency has been estimated at 1 in 137,401, partial biotinidase deficiency 1 in 109,921, and combined incidence of profound and partial biotinidase deficiency 1 in 61,067.
Biotinidase deficiency is more common in areas with a high rate of consanguinity (individuals who are blood relatives having children together, for example, first cousin marriages) such as Turkey and Saudi Arabia. The incidence of biotinidase deficiency also appears to be increased in Hispanic populations and lower in African American populations.
How good is newborn screening for biotinidase deficiency?
Almost all babies who have partial or profound biotinidase deficiency are detected in the US by routine newborn screening. It is possible that the initial newborn screening test might be a false positive (indicates a high risk of a baby being affected when they’re really not), especially in babies that are premature, or if the blood spot sample isn’t handled properly. It is important for any baby who has positive newborn screening for biotinidase deficiency to have follow-up confirmatory testing (measuring the amount of biotinidase enzyme activity in the blood).
If you have questions about the results of your baby’s newborn screening test, you can ask your child’s pediatrician for more information, or consult with a geneticist. The National Society of Genetic Counselors website includes a searchable "Find A Genetic Counselor" directory that can help you locate genetic counselors throughout the US and Canada.
How does biotinidase deficiency run in families?
Biotinidase deficiency is inherited in an autosomal recessive fashion, which means that an affected individual has a biotinidase deficiency-related gene change on both of their two copies of the BTD gene. One copy of an individual’s BTD gene is inherited from each parent. If an individual has one copy of a BTD gene with the typical gene sequence ("normal") and one copy of a BTD gene with a biotinidase deficiency-related gene change ("mutation"), they are referred to as a carrier. Carriers of biotinidase deficiency have enough working biotinidase enzyme that they are unaffected with biotinidase deficiency. Carriers of biotinidase deficiency may pass on either their working or nonworking copy of their BTD gene (1/2 or 50% chance of either). If both parents are carriers of a single biotinidase deficiency-related gene change, then with each pregnancy there is a ¼ (25%) chance of the baby being affected with biotinidase deficiency, a ½ (50%) chance of the baby being a carrier of a single biotinidase deficiency-related gene change, and a ¼ (25%) chance of the baby being neither affected nor a carrier of biotinidase deficiency.
Since individuals who are affected with biotinidase deficiency have biotinidase deficiency-related gene changes on both copies of their BTD gene, all of their children will receive a biotinidase deficiency-related gene change from them and be, at a minimum, carriers of biotinidase deficiency. Whether or not they are affected with biotinidase deficiency will depend on the carrier status of their other parent.
If both parents in a couple are affected with biotinidase deficiency, then all of their children will also be affected.
Since individuals who are carriers of biotinidase deficiency do not show any symptoms of the condition, it is common for an individual to have no way of knowing that they are a carrier of biotinidase deficiency unless they have an affected family member or child.
If you have questions about your reproductive risks and options related to biotinidase deficiency, you can locate genetic counselors throughout the United States and Canada on the "Find A Genetic Counselor" searchable directory on the National Society of Genetic Counselors website.
How do I give money to help research in biotinidase deficiency?
There are multiple support and education organizations related to newborn screening, inborn errors of metabolism and patient support and educational organizations that include biotinidase deficiency. If you are considering donating to a specific group or organization, http://www.charitynavigator.org provides information on over 8000 American organizations, including rating the organization’s financial health as well as accountability and transparency.
How do I get tested for biotinidase deficiency?
Most newborns born in the United States have newborn screening, and biotinidase deficiency is a recommended condition to be included in routine newborn screening. If you have questions about what conditions your state screens newborns for, and whether biotinidase deficiency is included, the Save Babies through Screening website provides links to state specific newborn screening information.
For diagnostic testing for biotinidase deficiency beyond the newborn period, you can discuss this testing with your primary care physician or geneticist. Biotinidase deficiency can be confirmed by either biochemical or molecular testing on blood.
For biochemical testing for biotinidase deficiency, the amount of biotinidase enzyme activity is measured in the blood. Individuals with biotinidase activity less than 10% of the normal average are diagnosed with profound biotinidase deficiency, while individuals with biotinidase activity 10-30% of the normal average are diagnosed with partial biotinidase deficiency. The diagnosis of profound or partial biotinidase deficiency can be made by biochemical (enzyme testing alone).
Molecular testing can also be used to diagnose biotinidase deficiency. The BTD gene is the name of the gene involved in biotinidase deficiency, and spelling errors in the BTD gene detected by sequencing of the gene are found in approximately 99% of individuals with biotinidase deficiency. BTD gene deletion/duplication can be done if gene sequencing does not identify two gene changes in affected individuals.
Genetic counselors may help you understand your testing options for biotinidase deficiency. The National Society of Genetic Counselors website includes a searchable "Find A Genetic Counselor" online directory to assist you in locating genetic counselors throughout the United States and Canada.
How do I find clinical research in biotinidase deficiency?
The website clinicaltrials.gov is a registry and results database of both publicly and privately supported clinical trials in human participants and includes sites around the world. Search "biotinidase deficiency" for updated information about possible clinical research opportunities related to biotinidase deficiency.
How do I find an expert, experienced doctor or team who takes care of individuals with biotinidase deficiency?
Geneticists and metabolic specialists have specialized training and expertise in managing the care of individuals with inherited metabolic conditions, including biotinidase deficiency. Geneticists/metabolic specialists and genetic counselors work as a team to answer your questions, discuss testing, identify your at-risk family members, and develop a comprehensive evaluation and treatment plan for you. They will work with your current doctors to organize the treatment, tests, and specialists you need.
To assist in locating genetic services in your area, the National Society of Genetic Counselors website includes a searchable "Find A Genetic Counselor" directory which may be used to locate genetic counselors throughout the United States and Canada.
Does anything make biotinidase deficiency worse?
The amount of biotinidase enzyme activity present in an individual is coded for by the BTD gene. However, individuals with biotinidase deficiency should avoid eating raw eggs. There is a specific protein found in egg whites called avidin. Avidin binds biotin and makes it unavailable to the body. Since individuals with biotinidase deficiency already have less free biotin available in their body than normal, they should avoid eating raw eggs in order to not have avidin bind up free biotin that might otherwise be available to their bodies. Cooking eggs inactivates avidin so it no longer binds biotin, and so it is fine for individuals with biotinidase deficiency to eat cooked eggs.
Do individuals with biotinidase deficiency need to follow a special diet?
Treatment of biotinidase deficiency is by lifelong daily oral free biotin supplementation, generally dosed at 5-10 mg daily. Individuals with biotin deficiency do not need to follow a special diet, other than avoiding consuming raw eggs. There is a specific protein found in egg whites called avidin. Avidin binds biotin and makes it unavailable to the body. Since individuals with biotinidase deficiency already have less free biotin available in their body than normal, they should avoid eating raw eggs in order to not have avidin bind up free biotin that might otherwise be available to their bodies. Cooking eggs inactivates avidin so it no longer binds biotin, and so it is fine for individuals with biotinidase deficiency to eat cooked eggs.
Can I buy biotin in liquid form?
While pharmacies may be able to dispense biotin as a solution or syrup, it is not recommended that liquid preparations of biotin be used in the treatment of biotinidase deficiency, as the suspension tends to settle and grow bacteria and there is an increased risk of inconsistent dosage.
For infants or young children unable to swallow tablets or capsules, it is recommended that the tablet be crushed/the capsule be opened and mixed with a small amount of breast milk or formula in a spoon, medicine dispenser, or syringe. It is recommended that the biotin not be put in a bottle, but rather in a small amount of liquid that can be consumed in full all at once.
At what age do symptoms of untreated biotinidase deficiency occur?
Individuals with untreated profound biotinidase deficiency can be expected to develop symptoms from the first week of life up to 10 years of age. The average age for development of symptoms is around three and a half months. There are reports of individuals with late onset profound biotinidase deficiency who did not develop symptoms until around adolescence.
Individuals with untreated partial biotinidase deficiency may develop symptoms only at a time when the body is under stress, such as during an illness or infection.
There are reports of individuals with untreated biotinidase deficiency who were apparently asymptomatic when diagnosed in adulthood.
Are there other names for biotinidase deficiency?
Biotinidase deficiency is most often referred to as biotinidase deficiency, classified as either profound or partial. Other names for biotinidase deficiency may also include:
Are there organ specific treatments to treat biotinidase deficiency?
Individuals with symptoms related to biotinidase deficiency may benefit from symptomatic management with appropriate specialists. Specifically, individuals with treated biotinidase deficiency should have yearly vision and hearing evaluations and regular physical examination by a doctor or metabolic specialist familiar with biotinidase deficiency. Individuals with biotinidase deficiency should be monitored by their physician for symptoms of biotinidase deficiency such as vision or hearing problems, skin problems, and developmental problems, as early interventions with any potential symptoms may improve outcome.
The best way to obtain the most accurate, current, clear, and comprehensive information about treatment and management of biotinidase deficiency is to be seen by a geneticist or metabolic specialist. Geneticists/metabolic specialists and genetic counselors work as a team to answer your questions, discuss testing, identify your at-risk family members, and develop a comprehensive evaluation and treatment plan for you. They will work with your current doctors to organize the treatment, tests, and specialists you need.
To assist in locating genetic services in your area, the National Society of Genetic Counselors website includes a searchable "Find A Genetic Counselor" directory which may be used to locate genetic counselors throughout the United States and Canada. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website. If you are looking for a metabolic clinic for treatment in the United States, you can search for the clinic or clinics in your state. A metabolic dietician can be found through the Genetic Metabolic Dieticians International webpage.
Are there one or two characteristic "odd" or "unusual" symptoms or clinical features of biotinidase deficiency?
Many of the symptoms potentially associated with untreated biotinidase deficiency are not specific to biotinidase deficiency and may be found in many other genetic or inherited metabolic conditions. However, there are a few potential symptoms of untreated profound biotinidase deficiency that are less commonly seen with other conditions and may be a clue to diagnosis, including eczema (skin rash), alopecia (hair loss), conjunctivitis (pink eye), candidiasis (a fungal infection), and ataxia (balance, coordination, and movement problem).
If you are concerned that you or your child may have symptoms of biotinidase deficiency, you should consult with your doctor or locate genetic services in your area. The National Society of Genetic Counselors website includes a "Find A Genetic Counselor" search tool which can help you locate a genetic counselor in the United States or Canada.
Are there different types of biotinidase deficiency?
Biotinidase deficiency can be classified as profound or partial, depending upon the amount of biotinidase enzyme activity present. When an individual has less than 10% of normal biotinidase activity present, it is classified as profound biotinidase activity. Individuals with 10-30% of normal biotinidase activity are referred to as having partial biotinidase activity. Left untreated, profound biotinidase activity is a more severe condition than partial biotinidase activity.
The amount of biotinidase activity can be determined in an individual by specialized blood tests, ordered by a physician.
Are there any other diseases that look a lot like biotinidase deficiency?
The symptoms that can occur in individuals with untreated biotinidase deficiency are nonspecific and can occur in many different conditions, including many inherited metabolic diseases. These symptoms may include vomiting, low muscle tone, and seizures, as well as laboratory findings involving the amount of ammonia or lactate present in the blood or urine.
Symptoms that can occur in untreated biotinidase deficiency may also be indicative of disorders such as isolated carboxylase deficiency, nutritional biotin deficiency, holocarboxylase synthetase deficiency, zinc deficiency, and essential fatty acid deficiency.
In addition to consultation with your primary care doctor, a metabolic specialist or medical geneticist can order the appropriate laboratory testing to diagnose biotinidase deficiency. To assist in locating genetic services in your area, the National Society of Genetic Counselors website includes a searchable "Find A Genetic Counselor" directory which may be used to locate genetic counselors throughout the United States and Canada.
Are all of the symptoms of untreated profound biotinidase deficiency reversible with initiation of treatment?
While individuals with symptoms related to untreated biotinidase deficiency are expected to improve with the initiation of lifelong daily oral biotin supplementation, and asymptomatic individuals are expected to remain asymptomatic if biotin therapy is continued, not all of the symptoms of untreated biotinidase deficiency are reversible. If an individual with untreated biotinidase deficiency develops more advanced symptoms such as vision problems, hearing loss and/or developmental delay, these symptoms are usually irreversible. It is still important, however, to treat individuals with symptoms related to biotinidase deficiency, as treatment is expected to improve other symptoms potentially related to untreated biotinidase deficiency, and possibly prevent other complications from occurring.
